Genetic Variant DAAM2:c.1361-43A>G (chr6-39878361-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001201427.2(DAAM2):c.1361-43A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 1,607,492 control chromosomes in the GnomAD database, including 272,058 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.58 ( 25802 hom., cov: 32)

Exomes 𝑓: 0.58 ( 246256 hom. )

Consequence

DAAM2
NM_001201427.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.161

Publications

12 publications found

Variant links:

Genes affected

DAAM2 (HGNC:18143): (dishevelled associated activator of morphogenesis 2) Predicted to enable actin binding activity and small GTPase binding activity. Predicted to be involved in nervous system development and regulation of Wnt signaling pathway. Predicted to act upstream of or within determination of left/right symmetry. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

DAAM2 links:

DAAM2-AS1 (HGNC:40830): (DAAM2 antisense RNA 1)

DAAM2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAAM2	NM_001201427.2 link	c.1361-43A>G		intron_variant	Intron 12 of 24	ENST00000274867.9	NP_001188356.1	Q86T65-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAAM2	ENST00000274867.9 link	c.1361-43A>G		intron_variant	Intron 12 of 24	1	NM_001201427.2	ENSP00000274867.4		Q86T65-3

Frequencies

GnomAD3 genomes

AF:

0.580

AC:

88039

AN:

151822

Hom.:

25768

Cov.:

show subpopulations

Gnomad AFR

AF:

0.559

Gnomad AMI

AF:

0.727

Gnomad AMR

AF:

0.571

Gnomad ASJ

AF:

0.578

Gnomad EAS

AF:

0.788

Gnomad SAS

AF:

0.692

Gnomad FIN

AF:

0.612

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.564

Gnomad OTH

AF:

0.582

GnomAD2 exomes

AF:

0.605

AC:

146265

AN:

241708

AF XY:

0.608

show subpopulations

Gnomad AFR exome

AF:

0.562

Gnomad AMR exome

AF:

0.571

Gnomad ASJ exome

AF:

0.579

Gnomad EAS exome

AF:

0.799

Gnomad FIN exome

AF:

0.607

Gnomad NFE exome

AF:

0.572

Gnomad OTH exome

AF:

0.573

GnomAD4 exome

AF:

0.580

AC:

843764

AN:

1455552

Hom.:

246256

Cov.:

AF XY:

0.583

AC XY:

421604

AN XY:

723372

show subpopulations

African (AFR)

AF:

0.571

AC:

19043

AN:

33378

American (AMR)

AF:

0.570

AC:

25076

AN:

44014

Ashkenazi Jewish (ASJ)

AF:

0.575

AC:

14865

AN:

25862

East Asian (EAS)

AF:

0.737

AC:

29154

AN:

39554

South Asian (SAS)

AF:

0.678

AC:

57993

AN:

85558

European-Finnish (FIN)

AF:

0.600

AC:

31899

AN:

53134

Middle Eastern (MID)

AF:

0.600

AC:

3448

AN:

5742

European-Non Finnish (NFE)

AF:

0.565

AC:

626602

AN:

1108190

Other (OTH)

AF:

0.594

AC:

35684

AN:

60120

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

20476

40952

61429

81905

102381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17638

35276

52914

70552

88190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.580

AC:

88121

AN:

151940

Hom.:

25802

Cov.:

AF XY:

0.583

AC XY:

43323

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.560

AC:

23184

AN:

41432

American (AMR)

AF:

0.571

AC:

8720

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.578

AC:

2007

AN:

3472

East Asian (EAS)

AF:

0.787

AC:

4067

AN:

5166

South Asian (SAS)

AF:

0.691

AC:

3314

AN:

4798

European-Finnish (FIN)

AF:

0.612

AC:

6451

AN:

10542

Middle Eastern (MID)

AF:

0.582

AC:

171

AN:

294

European-Non Finnish (NFE)

AF:

0.564

AC:

38305

AN:

67930

Other (OTH)

AF:

0.587

AC:

1239

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1894

3787

5681

7574

9468

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

756

1512

2268

3024

3780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.572

Hom.:

68452

Bravo

AF:

0.578

Asia WGS

AF:

0.737

AC:

2567

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.21

(source)

DANN

Benign

0.67

PhyloP100

0.16

Mutation Taster

=21/79

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over